Lipofuscin
showing lipofuscin in a liver biopsy with ground glass hepatocytes. H&E stain.]] Lipofuscin is the name given to finely granular yellow-brown pigment granules composed of lipid-containing residues of lysosomal digestion. It is considered one of the aging or "wear and tear" pigments, found in the liver, kidney, heart muscle, adrenals, nerve cells, and ganglion cells. It is specifically arranged around the nucleus. Formation and turnover It appears to be the product of the oxidation of unsaturated fatty acids, and may be symptomatic of membrane damage, or damage to mitochondria and lysosomes. Aside from a large lipid content, lipofuscin is known to contain sugars and metals, including mercury, aluminum, iron, copper and zinc.Chris Gaugler, "Lipofuscin", Stanislaus Journal of Biochemical Reviews May 1997 The accumulation of lipofuscin-like material may be the result of an imbalance between formation and disposal mechanisms: Such accumulation can be induced in rats by administering a protease inhibitor (leupeptin); after a period of three months, the levels of the lipofuscin-like material return to normal, indicating the action of a significant disposal mechanism. ML Katz, LM Rice and CL Gao, "Reversible accumulation of lipofuscin-like inclusions in the retinal pigment epithelium", Investigative Ophthalmology & Visual Science, Vol 40,(1999) pp.175-181. However, this result is controversial, as it is questionable if the leupeptin-induced material is true lipofuscin.Alexei Terman and Ulf T. Brunk, "Is Lipofuscin Eliminated from Cells?", Investigative Ophthalmology and Visual Science, (1999) vol. 40 pp.2463-2464.Sallyanne Davies and Steven Ellis, "Lipofuscin Turnover", Investigative Ophthalmology and Visual Science. (1999)40 pp.1887-1888 There exists evidence that "true lipofuscin" is not degradable in vitro''Terman, A, Brunk, UT (1998) "On the degradability and exocytosis of ceroid/lipofuscin in cultured rat cardiac myocytes", ''Mech Ageing Dev 100, pp.145-156Terman, A, Brunk, UT (1998) "Ceroid/lipofuscin formation in cultured human fibroblasts: the role of oxidative stress and lysosomal proteolysis", Mech Ageing Dev 104, pp.277-291Elleder, M, Drahota, Z, Lisa, V, et al. (1995) "Tissue culture loading test with storage granules from animal models of neuronal ceroid-lipofuscinosis (Batten disease): testing their lysosomal degradability by normal and Batten cells" Am J Med Genet 57, pp.213-221; whether this holds in vivo over longer time periods is not clear. Relation to diseases Lipofuscin accumulation is a major risk factor implicated in macular degeneration, a degenerative disease of the eye.John Lacey, "Harvard Medical signs agreement with Merck to develop potential therapy for macular degeneration", 23-May-2006 Abnormal accumulation of lipofuscin is associated with a group of diseases of neurodegenerative disorder type called lipofuscinoses, e.g., neuronal ceroid lipofuscinosis, also known as Batten disease, as well as some other names. Pathological accumulation of lipofuscin is implicated in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, certain lysosomal diseases, acromegaly, denervation atrophy, lipid myopathy, chronic obstructive pulmonary diseaseMuscle Nerve (2002) vol 25 pp.383-389, centronuclear myopathy. Accumulation of lipofuscin in the colon is the cause of the condition melanosis coli. Possible therapies to reduce lipofuscin accumulation Calorie restriction, vitamin E,, and increased glutathione appear to reduce or halt the production of lipofuscin. The nootropic drug piracetam appears to significantly reduce accumulation of lipofuscin in the brain tissue of rats. Paula-Barbosa, M. et al., "The effects of Piracetam on lipofuscin of the rat cerebellar and hippocampa; neurons after long-term alcohol treatment and withdrawal", Alcoholism: Clinical and Experimental Research 15, (1991) pp. 834-838. Other possible treatments: *CentrophenoxineRoy D, Pathak DN, Singh R., "Effect of centrophenoxine on the antioxidative enzymes in various regions of the aging rat brain.", Exp Gerontol. 1983;18(3):185-97. *Acetyl-L-Carnitine Amenta F, Ferrante F, et all, "Reduced lipofuscin accumulation in senescent rat brain by long-term acetyl-L-carnitine treatment.", Arch Gerontol Geriatr. 1989 Sep-Oct;9(2):147-53. *Ginko Biloba Huang SZ, Luo YJ, Wang L, Cai KY., "Effect of ginkgo biloba extract on livers in aged rats. ", World J Gastroenterol. 2005 Jan 7;11(1):132-5. *DMAE http://www.dmae.org/herbal-remedies/dmae/DMAE-benefits Wet macular degeneration can be treated using Selective Photothermolysis where a pulsed unfocused laser prodominantly heats and kills pigment (ie: lipofuscin) rich cells, leaving untouched healthy cells to multiply and fill in the gaps. The technique is also used as a skin treatment to remove tattoos, liverspots, and generally make skin appear younger. This ability to selectively target lipofuscin has opened up research opportunities in the field of Anti-aging medicine. References External links for general reviews *Chris Gaugler, "Lipofuscin", Stanislaus Journal of Biochemical Reviews May 1997 * *Histology at neuro.wustl.edu * *Destroying Lipofuscin and Destroying Cancer, FightAging.org *Unfocused Pulsed Lasers Selectively Destroy Lipofuscin, AcceleratingFuture.com Category:Biomolecules Category:Aging